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Evolutionary Therapy for Rhabdomyosarcoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04388839
Recruitment Status : Recruiting
First Posted : May 14, 2020
Last Update Posted : September 7, 2020
Sponsor:
Collaborator:
National Pediatric Cancer Foundation
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute

Brief Summary:
This clinical trial will evaluate 4 different strategies of chemotherapy schedules in newly diagnosed participants with metastatic Fusion Positive (alveolar) Rhabdomyosarcoma. The participant and their physician will choose from: Arm A) a first strike therapy, Arm B) a first strike-second strike (maintenance) therapy, Arm C) an adaptively timed therapy, and Arm D) conventional chemotherapy.

Condition or disease Intervention/treatment Phase
Rhabdomyosarcoma Drug: Vincristine Drug: Cyclophosphamide Drug: Vinorelbine Drug: Actinomycin D Drug: Cyclophosphamide Pill Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 28 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Evolutionary Inspired Therapy for Newly Diagnosed, Metastatic, Fusion Positive Rhabdomyosarcoma
Actual Study Start Date : September 3, 2020
Estimated Primary Completion Date : December 2026
Estimated Study Completion Date : December 2027

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Arm A - First Strike
Participants will receive 42 weeks of conventional doses of vinorelbine, actinomycin D and cyclophosphamide
Drug: Cyclophosphamide
IV over 60 minutes with dosing ranging from 220mg to 1200mg

Drug: Vinorelbine
IV push over 6-10 minutes with dosing ranging from 4mg-25mg
Other Name: Navelbine

Drug: Actinomycin D
Actinomycin D should not be given with radiation. Will be administered through IV over 3-5 minutes with dosing ranging from 0.025mg-0.045mg
Other Name: Cosmegen

Experimental: Arm B - Second Strike - Maintenance
Participants will receive conventional doses of Vincristine/Actinomycin D/Cyclophosphamide (VAC) until complete response (CR) for 12-42 weeks and then switch to up to 2 years of vinorelbine/oral cyclophoshamide
Drug: Vincristine
IV push over 1 minute with dosing ranging from 0.24mg up to 1.5mg

Drug: Cyclophosphamide
IV over 60 minutes with dosing ranging from 220mg to 1200mg

Drug: Vinorelbine
IV push over 6-10 minutes with dosing ranging from 4mg-25mg
Other Name: Navelbine

Drug: Actinomycin D
Actinomycin D should not be given with radiation. Will be administered through IV over 3-5 minutes with dosing ranging from 0.025mg-0.045mg
Other Name: Cosmegen

Drug: Cyclophosphamide Pill
Based on Body Surface Area (BSA) round to nearest 25mg

Experimental: Arm C - Adaptive Therapy
Therapy with VAC that starts and stops based on response, adaptive timing of therapy, with a prolonged time to progression rather than complete remission goal
Drug: Vincristine
IV push over 1 minute with dosing ranging from 0.24mg up to 1.5mg

Drug: Cyclophosphamide
IV over 60 minutes with dosing ranging from 220mg to 1200mg

Drug: Actinomycin D
Actinomycin D should not be given with radiation. Will be administered through IV over 3-5 minutes with dosing ranging from 0.025mg-0.045mg
Other Name: Cosmegen

Active Comparator: Arm - D Conventional Therapy
Participants will receive a chemotherapy combination based on published trials. An example would be 42 weeks of VAC but may also include irinotecan, doxorubicin, ifosfamide, etoposide.
Drug: Vincristine
IV push over 1 minute with dosing ranging from 0.24mg up to 1.5mg

Drug: Cyclophosphamide
IV over 60 minutes with dosing ranging from 220mg to 1200mg

Drug: Actinomycin D
Actinomycin D should not be given with radiation. Will be administered through IV over 3-5 minutes with dosing ranging from 0.025mg-0.045mg
Other Name: Cosmegen




Primary Outcome Measures :
  1. First Strike Event Free Survival [ Time Frame: Baseline to 3 years ]
    Participants who choose the first strike treatment will have event free survival assessed at 3 years after initiating treatment. Event free survival is defined as time from treatment initiation to event which includes (1) any recurrence (local or regional, or distant) and (2) death due to any cause.

  2. Second Strike Event Free Survival [ Time Frame: Baseline to 3 years ]
    Participants who choose the second strike treatment will have event free survival assessed at 3 years after initiating treatment. Event free survival is defined as time from treatment initiation to event which includes (1) any recurrence (local or regional, or distant) and (2) death due to any cause

  3. Adaptive Therapy Event Free Survival [ Time Frame: Baseline to 3 years ]
    Participants who choose the adaptive therapy will have event free survival assessed at 3 years after initiating treatment. Event free survival is defined as time from treatment initiation to event which includes (1) progression that does not respond to additional VAC dosing and (2) death due to any cause


Secondary Outcome Measures :
  1. Overall Survival [ Time Frame: 5 years ]
    The time to event endpoint of overall survival is defined as the duration of time from diagnosis to death or last follow-up, where event would be death from any cause

  2. Treatment-related adverse events of a certain grade or higher [ Time Frame: Baseline to 5 years ]
    Number of participants with treatment-related adverse events of a certain grade or higher and hematological/biochemical toxicities based on laboratory measurements as assessed by CTCAE v5.0



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Participants must have a new histologic diagnosis of rhabdomyosarcoma
  • Participants must have FISH, PCR or other molecular confirmation of PAX/FOXO1 fusion per institutional standards
  • Participants must have sufficient tissue (up to 10 unstained FFPE) for correlative testing
  • All participants must have distant metastatic disease; either biopsy positive or PET avid extranodal lesions determined by the investigator to be metastatic disease. Patients with a single distant metastatic site that has been excised prior to study entry are eligible
  • No prior systemic chemotherapy
  • Participants enrolled to Arm B, maintenance, must be able to take oral cyclophosphamide. Note: enteral administration of cyclophosphamide is allowable.
  • Pregnancy or Breast Feeding: Pregnant or breast-feeding women will not be entered on this study, because there is no available information regarding human fetal or teratogenic toxicities. Females of childbearing potential must have a negative serum or urine pregnancy test within 24 hours of starting protocol therapy.
  • Males and females of reproductive potential may not participate unless they have agreed to the use of, at minimum, two methods of contraception during and after treatment.
  • Women of childbearing potential should adhere to contraception for a period of 4 months after completion of systematic chemotherapy administration
  • Men who are sexually active with women of child bearing potential should adhere to contraception for a period of 4 months after completion of systematic chemotherapy administration
  • All patients and/or their parents or legal guardians must have the ability to understand and the willingness to sign a written informed consent or assent document.

Exclusion Criteria:

  • Participants with regional lymph nodes as the only site of disease are not eligible. Distant nodal sites alone would be eligible
  • Participants who are receiving any other investigational agents for rhabdomyosarcoma are ineligible
  • Participants must not be receiving any additional medicines being given for the specific purpose of treating cancer. Alternative medications including, but not limited to cannabis based products would not be a reason for exclusion
  • Participants are ineligible if they have uncontrolled intercurrent illness including, but not limited to:

    • ongoing or active infection not expected to resolve with current antibiotic plan
    • cardiac arrhythmia
    • psychiatric illness/social situations that would limit compliance with study requirements
  • Participants who are considered unable to comply with the safety monitoring requirements of the study are not eligible

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04388839


Contacts
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Contact: Jessica Crimella, BSN, RN 813-745-6250 Jessica.Crimella@moffitt.org
Contact: Stella Valavanis, MPH 813-745-6986 Stella.Valavanis@moffitt.org

Locations
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United States, Florida
Moffitt Cancer Center Recruiting
Tampa, Florida, United States, 33612
Contact: Jessica R Crimella, BSN, RN    813-745-6250    Jessica.Crimella@moffitt.org   
Principal Investigator: Damon R Reed, MD         
Sponsors and Collaborators
H. Lee Moffitt Cancer Center and Research Institute
National Pediatric Cancer Foundation
Investigators
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Principal Investigator: Damon Reed, MD Moffitt Cancer Center
Additional Information:
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Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier: NCT04388839    
Other Study ID Numbers: MCC-20339
First Posted: May 14, 2020    Key Record Dates
Last Update Posted: September 7, 2020
Last Verified: September 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by H. Lee Moffitt Cancer Center and Research Institute:
Soft Tissue Cancer
Skeletal Muscle Tissue Cancer
Sarcoma
Additional relevant MeSH terms:
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Rhabdomyosarcoma
Myosarcoma
Neoplasms, Muscle Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Sarcoma
Dactinomycin
Cyclophosphamide
Vincristine
Vinorelbine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Protein Synthesis Inhibitors
Enzyme Inhibitors
Nucleic Acid Synthesis Inhibitors